Drug researchers will soon be able to screen tens of thousands of existing compounds from multiple drug libraries to see how well they work against Covid-19 under an NIH tool in development.
The National Institutes of Health this week issued a contract to test existing antivirals against the SARS-Cov-2 virus in a high-level biocontainment laboratory. The National Center for Advancing Translational Sciences (NCATS), the NIH unit that solicited the contract, is charged with delivering effective treatments to patients quickly.
“We need to be able to screen better. We need multiple tools in our toolbox,” NCATS staff scientist Kirill Gorshkov said in an interview.
While vaccine development happened at a record-breaking pace, efforts to repurpose existing drugs into successful antivirals for SARS-Cov-2 haven’t been as successful. The Food and Drug Administration approved
Ultimately, the NCATS scientists want to improve ways to identify potentially successful drugs earlier in the screening process, which would avoid human experimentation on ineffective treatments through costly clinical trials. The high failure rate in drug discovery is a well-known problem that existed long before the pandemic.
“If we can show that a drug, through through screening and through different experiments, has an antiviral effect different ways, we can be more confident that it’s effective,” Gorshkov said.
Cells From a Monkey
Gorshkov and his colleagues Wei Zheng, biology leader in the NCATS division, and scientist Catherine Chen, are working with a standard cell line used in pre-clinical research known as VeroE6, derived from the kidney of an African green monkey. The screening system will start with a test of how much of the live virus they need to put into those cells so they can tell whether a repurposed drug works to reduce the viral load.
They plan to use remdesivir as the control compound because they know it reduces the ability of the virus to replicate, and other drugs can be compared against those results. Once the platform is running, scientists can generate raw data on repurposed drugs in one to two days.
“The whole goal of this is to find more effective candidate compounds at the pre-clinical level, and then move those forward to other more advanced testing,” Gorshkov said. “If finding the drug in cells always translated to human efficacy, we would fix all of the diseases really quickly. But it’s actually pretty challenging because of the nuances of the human body, human physiology.”
Gorshkov’s work focuses on pre-clinical testing, and it could help improve the drug development process by doing a better job of weeding out unsuccessful therapies before they hit clinical trials.
The clinical trial system has come under criticism from Janet Woodcock, the nation’s top drug regulator, who has called for “very serious soul searching.”
Just 6% of Covid clinical trials have yielded results the FDA deems actionable. There’s a lot less evidence “than we could have had, and that the system could have delivered had it been more organized, more focused on the societal role and generally more effective,” Woodcock said at a National Academies panel last month.
Fewer than 10% of all drugs that make it to the initial stage of human testing ever come to market, according to a report from the Biotechnology Innovation Organization, an industry trade group.
—With assistance from Shira Stein